This invention relates to a thermostated block for laboratory thermostats having wells to receive and make large-area contact with segments of liquid sample filled vials and having heat regulating devices making good thermal contact with the block to generate different temperatures at different sites of the block.
Such a thermostated block is known from U.S. Pat. No. 5,525,300. Two heat-regulating devices in thermal contact with the thermostated block at two of its opposite ends heat it at one end and cool it at the other. A thermal flow runs longitudinally between the heat regulating devices through the thermostated block so that a temperature profile is generated in the longitudinal block direction, resulting in different temperatures. A thermostated block generating such a temperature gradient allows ascertaining the optimal temperature, for instance, in the polymerase chain reaction (PCR) for a temperature stage in this process.
Controlling the temperature of the thermostated block solely at its ends, however, has a drawback. When turning the apparatus ON or when the temperature to be set in the thermostated block changes, the thermostating time delays to the desired equilibrium are substantial on account of the two-end thermostating. Furthermore, the temperature at the middle of the thermostated block may deviate from the desired temperature profile due to environmental effects.
An object of the present invention is to provide a thermostated block of the above type which allows achieving the desired temperature profile faster and without problems.
In accordance with the invention, several heat-regulating devices acting on the thermostated block make contact over a large surface with adjoining zones of the contact side. This design is remarkable in that despite the large-area contact with the heat-regulating devices uniformly supplying heat to or dissipating it from the thermostated block, the heat-regulating devices also can be used to set up a temperature gradient easily. The known end configuration of the heat regulating devices is not required for this purpose. The design of the invention offers the advantage of direct temperature control of the thermostated block over its entire surface. Environmental effects, for instance from the ambient air, are substantially excluded. Because of the large-area action across the full surface of the thermostated block, the times needed to reach the desired temperature profile also are substantially less, for instance, when the thermostated block must be switched from a temperature profile in the range of 40xc2x0 C. to a temperature profile in the range of 90xc2x0 C. Accordingly, it is easily feasible to change sequentially the sample temperature in a thermostated block to a different temperature level, either using a temperature gradient or alternatively using a temperature which is uniform over the entire block.
In an alternative operation, the large-area contact implemented by the heat regulating devices can be used in a very simple manner to uniformly thermostat all wells. Unlike the initially cited design of the prior art, this design of the invention does not require adding at the contact side another heat regulating device to the cooling and heating regulating devices at the ends of the thermostated block.
By providing segments at boundaries between zones of the block with different thermal impedances, the heat passing between adjacent heat-regulating devices in the thermostated block may be reduced. Effects from such heat flow between the regulating means driving the heat-regulating devices that might result in regulation oscillations are reduced thereby and the complexity of electronic regulation is decreased.
The temperature profile across the thermostated block, namely the particular temperature gradient, does not always correspond to the desired temperature profile. Deviations arise in particular at the ends of the thermostated block where the effect of the adjacent heat-regulating devices is less and thus the temperature gradient is shallower. Using such segments of different thermal conductivities allows correcting the temperature curve. In particular, a higher temperature gradient may be achieved using a higher thermal impedance, and thereby the shallow gradients at the ends may be corrected.
In an advantageous manner, the segments of the thermostated block increase in thermal impedance from its center toward its edge. As a result the temperature profile can be linearized.
The segments can be formed as are grooves which by merely reducing the local, material cross-section produce a higher thermal impedance. In contrast to the known cross-boreholes found for such purposes in the initially cited design of the state of the art, the invention""s configuration offers easier manufacture and a more advantageous geometry between wells in the form of recesses.
Dividing the contact side of the block longitudinally and transversely into zones making contact with separate heat regulating devices is also advantageous. The heat regulating devices distributed across the surface may be operated in a variety of ways. Laterally adjacent heat-regulating devices may be operated to be identically thermostating so that a temperature gradient is set up in the longitudinal or in the transverse direction of the thermostated block. Illustratively, a gradient may be set up in a thermostated block at different temperature levels in different directions. Also, the heat-regulating devices each may be operated differently so that a temperature gradient may be set up as well in the x-direction as in the y-direction, for instance with different temperature gradients in the two directions.
Two different types of laboratory vials may be used without having to convert the laboratory thermostats. Even mixed outfitting is possible. The large number of closely adjoining recesses in the form of wells allows lowering the mass of the thermostated block. As a result the heat capacity of the block is lowered and the temperature may be raised more rapidly to the desired temperature. Moreover it is also possible to make the thermostated block thinner toward its wells side whereby the heat between the heat-regulating devices preferably follows a path through a plate-region of the thermostated block adjacent to the contact side, and as a result the desired temperature can be set very accurately and uniformly. Thereby, the wells of one type are made to match a predetermined grid arrangement of vials. Hence, vials also may be used which illustratively are integrated into a continuous plate configuration. The desired thinning of the upper part of the thermostated block situated toward the receiving side may be enhanced by additional holes between the wells. A continuous plate of the thermostated block, running continuously underneath the wells and holes, increases the uniformity of the temperature setting. Segments having higher thermal impedances as are present in the initially cited conventional design in the form of boreholes may be used to correct the desired temperature profile. Advantageously such segments are in the form for instance of grooves running from the contact side and illustratively meandering between the wells and the holes.
The block together with another heat regulating device can be made displaceable relative to a plate holder supporting the vials and can be exchangeably moved to a position of alignment of the wells relative to the vials. As in the known design, they make it possible to subject the containers sequentially to various thermostated blocks thermostated at different levels and each having either a temperature gradient or a temperature constant across its surface. To allow sideways motion, the thermostated blocks may be mounted in a laterally displaceable carriage. They also may be mounted in a rotor for that purpose, the rotor illustratively rotating like a lazy Susan in a plane parallel to the holding means. Preferably, they are rotated together with a rotor about a shaft parallel to the holding means to allow especial compactness. The blocks may be displaced to move away from the rotor, or preferably the rotor is moved to effect separation as a whole.